Biology subjects

Sakai, Y.

Publications and source records attributed to Sakai, Y..

At least 19 recordsLinked to original sources

bioRxiv2026

Associated Bacteria, Particularly Mucilaginibacter Species, Inhibit Sheath Formation in Nostoc commune

The terrestrial cyanobacterium Nostoc commune fixes atmospheric nitrogen and exhibits remarkable desiccation tolerance, making it a promising organism for biomass production on land unsuitable for conventional agriculture. However, reliable artificial cultivation of N. commune remains difficult because hormogonium formation cannot yet be induced reproducibly and mechanically prepared trichome fragments often fail to develop into sheath-enclosed colonies. In this study, we examined factors affecting sheath formation in short non-motile trichome fragments, referred to here as nas-trichomes. Microscopic observation revealed two distinct developmental outcomes: a curling type, in which trichomes formed sheaths and developed into compact colonies, and an elongation type, in which trichomes extended without forming a distinct sheath. Curling-rich cultures were obtained only from colonies subjected to drying and rehydration, and early bacterial proliferation around trichomes was negatively associated with subsequent sheath formation. Microbial community analysis showed that Mucilaginibacter was enriched in elongation-rich cultures. Co-culture experiments further demonstrated that M. segetis, M. oryzae, M. jinjuensis, and M. xinganensis significantly inhibited sheath formation at high bacterial density. These results indicate that associated bacteria, particularly specific Mucilaginibacter species, can inhibit sheath formation in N. commune and suggest that controlling early bacterial proliferation is essential for establishing reliable cultivation methods.

microbiology↗

bioRxiv2026

The strength of a gene's first 5' splice site is a key determinant of its expression

The control of gene expression is central to cellular physiology and to various biotechnological applications. In higher eukaryotes, synthesis of most messenger RNAs involves removal of introns during splicing. Intron-containing genes are often more highly expressed than intronless versions, despite generating the same mRNA transcripts, suggesting that the splicing of transcripts from a gene positively impacts its expression. Termed intron-mediated enhancement (IME), this phenomenon has been observed in animals, plants, and fungi, with enhancement ranging from 2- to 100-fold and the strongest effects observed for promoter-proximal introns1-3. Here, we assayed thousands of natural human introns, covering all distinct human 5' splice site (5SS) motifs and thousands of 3' splice sites (3SS), for their ability to enhance (or repress) expression of a reporter gene. The results confirmed previous observations that intronic UUUU motifs augment the magnitude of IME, and revealed two fundamental features of IME: (i) only introns spliced by the major spliceosome elicit IME, with minor introns often repressing expression; and (ii) the magnitude of IME increases with the strength of the 5SS motif, but is independent of 3SS strength. Our findings imply that genetic variants that alter the strength of the first 5SS of genes may alter their expression by modulating IME without necessarily impacting splicing. We confirm this expectation using human population genetic data and further show that disease-relevant perturbations of U1 snRNP components that enhance recognition of subsets of first 5SS up-regulate expression of the associated genes. These findings demonstrate that recognition of the first 5SS is vitally important to the expression of human genes.

genetics↗

bioRxiv2026

A paralog of a clonal propagation regulator promotes cell-cycle re-entry during thallus regeneration in Marchantia polymorpha

Plants possess a remarkable capacity for regeneration, which involves the redeployment of developmental programs and diverse regulatory mechanisms. However, how related regulators with overlapping functions are differentially deployed during regeneration remains poorly understood. The model liverwort Marchantia polymorpha provides a powerful experimental system for studying regeneration because it readily regenerates apical meristems from basal thallus fragments after removal of the original meristem, even without exogenous plant hormones. Here, we identify the R2R3-MYB transcription factor GEMMA CUP-ASSOCIATED MYB1-LIKE (MpGC1L), the closest paralog of the clonal propagation regulator MpGCAM1, as a positive regulator of regeneration. MpGC1L was rapidly induced at the cut site following meristem removal. Ectopic overexpression of MpGC1L caused the proliferation of undifferentiated cells, whereas Mpgc1l mutants showed delayed regeneration and reduced S-phase entry. Loss of MpGCAM1 alone had little effect on regeneration but markedly enhanced the Mpgc1l phenotype, indicating partially redundant functions. Transcriptome analysis of the double mutant revealed reduced induction of genes associated with ribosome biogenesis and the cell cycle. We next examined the relationship between MpGC1L and the known jasmonate- and auxin- related regeneration regulators, MpERF15 and MpLAXR. MpGC1L induction was retained in Mperf15 and Mplaxr mutants and was unaffected by OPDA or auxin treatment, whereas MpERF15 and MpLAXR were still induced in Mpgc1l Mpgcam1 double mutants. Thus, these regulators are not arranged in a simple linear transcriptional pathway. Our findings reveal that the paralogous MYB transcription factors MpGC1L and MpGCAM1 promote cell proliferation in distinct developmental contexts, thereby linking clonal propagation and wound-induced regeneration.

plant biology↗

bioRxiv2026

RHO GTPase of Plants contributes to robust establishment of cellular asymmetry during development from a single cell

A fundamental question in developmental biology is how highly complex, yet reproducible multicellular body plans form from a single cell. The multicellular haploid body of the land plant Marchantia polymorpha develops from a single isolated cell - the spore - that divides asymmetrically. This produces a small terminally differentiating basal cell, and a large proliferative apical cell that gives rise to the multicellular sporeling body. The genetic basis for the establishment of asymmetry, first within the spore, and later within the sporeling body has remained virtually unknown. Here, we show that the plant specific RHO-type GTPase - RHO OF PLANTS (ROP) - polarises to the spore basal pole to ensure spore division is highly and reproducibly asymmetric. We demonstrate this highly asymmetric division is necessary to specify the terminal differentiation of the basal cell. Furthermore, we show that ROP-mediated polarised outgrowth is required to establish asymmetry within the sporeling body derived from the apical cell. Our discovery highlights how ROP function confers developmental robustness and contributes to the establishment of asymmetry during plant development from a single isolated cell.

plant biology↗

bioRxiv2026

A bistable UV-sensitive opsin from a reef building coral showing a switchable and tunable regulation of Gs-signaling by different wavelengths of light

Cnidarians possess large number of opsins in their genomes for their various photoreceptive functions. In particular, they uniquely possess Gs-coupled opsins that induce intracellular cAMP accumulation in a light-dependent manner. These Gs-coupled opsins, cnidopsins, are powerful optogenetic tools manipulating cAMP-dependent cellular responses. In this study, we characterized a cnidopsin, named as AtCnidop3a, from the coral Acropora tenuis as a Gs-coupled and UV-sensitive bistable pigment. This cnidopsin showed a large spectral shift upon activation from absorption maxima from 395 nm to 560 nm, and the resting and activated states are interconvertible by illumination with UV (or violet) and orange light. The activated state efficiently activated Gs proteins and elevated intracellular cAMP levels in mammalian cultured cells. To engineer the opsin mutant that can be turned on and off upon long wavelength light illumination by utilizing the large spectral separation, negatively charged amino acids were introduced near the retinal Schiff base region. Among tested opsin mutants, the Y1133.28E mutant is capable of being activated by green light unlike the wild-type while retaining the property of being inactivated by orange light like the wild-type, indicating successful conversion of the opsin to a visible light sensitive bistable pigment. The visible light-induced cAMP regulation of the Y1133.28E mutant was enhanced by an additional L942.61G substitution. Our characterization and engineering of the cnidopsin revealed functional diversity of cnidarian opsins and its potential utility as optogenetic tools regulating Gs-dependent physiological responses.

biochemistry↗

bioRxiv2026

Self-regenerating opsin from reef-building coral

Opsins underlie diverse physiological responses to light in animals. In the dark, most opsins bind the chromophore 11-cis retinal, which isomerizes to all-trans form upon light absorption, representing the initial key step in signaling. Maintenance of opsin function therefore requires continuous regeneration of the inactive, 11-cis-retinal-bound state. Here, we report a novel type of opsin, AtAntho2c, from a reef-building coral, whose active form, bound to all-trans retinal, can thermally revert to the initial dark state bound to 11-cis retinal. A cysteine residue in extracellular loop 2 region plays a key role in the self-regeneration ability. Using time-resolved and low-temperature spectroscopies, we identify two spectrally distinct photointermediates prior to the all-trans to 11-cis isomerization in AtAntho2c, whose formation rates and yields are found to vary depending on temperature and pH conditions. The active form of AtAntho2c activates Gi/o G protein, resulting in a transient and repeatable decrease in cellular cAMP levels upon repeated light stimulations, even in the absence of exogenous retinal in cultured cells. Furthermore, we confirm that cells expressing AtAntho2c exhibit membrane hyperpolarization via GIRK channel activation light-dependently. These properties highlight the potential of AtAntho2c as a versatile optogenetic actuator capable of repeatedly modulate Gi/o signaling without retinal supplementation. Significance StatementLight-sensitive proteins, opsins, form active states upon light absorption, leading to intracellular G protein signaling and various cellular outputs. The active states require specific enzymatic machinery or another photon absorption to regenerate inactive opsins ready to respond to repeated light stimuli and maintain continuous responsiveness. In our study, we identify and analyze a coral opsin of which the active state rapidly and autonomously reverts to the inactive state in the dark through thermal isomerization of the retinal chromophore within the opsin. This regeneration mechanism allows the opsin to respond to repeated light stimuli at high temporal resolution and maintain large signal amplitude without the need for exogenous retinal making this opsin potentially useful for developing versatile optogenetic tools.

biophysics↗

bioRxiv2026

Computational analysis reveals the requirement for cell-cell interaction in liver repopulation by transplanted hepatocytes

Hepatocyte transplantation is a promising alternative to liver transplantation; however, it currently serves only as a temporary treatment until a donor organ becomes available. In contrast, animal studies have demonstrated "liver repopulation", a phenomenon in which transplanted hepatocytes progressively replace host hepatocytes. Despite extensive documentation, the mechanisms driving this process remain poorly understood. More fundamentally, it remains unclear whether liver repopulation is driven by active cell-cell interactions between host and transplanted hepatocytes that induce host cell death, or whether it can be explained solely by intrinsic differences in proliferation and survival between these populations. To address this, we performed computational simulations using an agent-based model constrained by experimental data from repopulation in uninjured rat livers. Our analysis reveals that host hepatocyte death rate is the dominant determinant of repopulation kinetics, whereas variations in proliferation rate have only a limited impact. Notably, experimentally observed repopulation dynamics were only reproduced when cell- cell interactions were incorporated, or alternatively when host hepatocyte lifespan was set to unrealistically short values (approximately 25 days). These findings support a model in which cell- cell interactions play a critical role in efficient liver repopulation. More broadly, this study establishes a conceptual and computational framework for evaluating the requirement for cell-cell interactions in tissue replacement, even in the absence of a defined molecular mechanism.

systems biology↗

bioRxiv2026

CCAN forms the spherical shell-like structure in interphase kinetochores

The kinetochore is an essential structure for the faithful chromosome segregation during mitosis. The 16-protein complex known as the constitutive centromere-associated network (CCAN) localizes the kinetochore throughout the cell cycle and forms the basis of the kinetochore. Although a structural model of an individual CCAN unit has been proposed through cryo-electron microscopy analysis, little is known about how multiple CCAN units are organized within cells. Here, using in silico and in vivo analyses, we demonstrate that multiple CCAN units form a spherical, shell-like structure in interphase DT40 kinetochores. CENP-T and CENP-N localize to the CCAN shell, and the CENP-C cupin domain clusters at the center. Molecular dynamics simulations of CCAN assembly suggest that CENP-C contributes to the orientation of CCAN units, leading to the formation of a spherical shell-like structure via CENP-C oligomerization. Super-resolution imaging reveals the spherical shell-like structure at DT40 kinetochores, and knocking out CENP-C abolishes the structure, supporting the reliability of the predicted models. These findings provide important insights into the spatial organization of functional kinetochores within cells.

molecular biology↗

bioRxiv2025

Structural and mechanistic basis for membrane recognition and activation of the vacuolar lipase Atg15

Summary/Abstract Atg15 is a vacuolar phospholipase B essential for the degradation of intravacuolar vesicles such as autophagic bodies. Despite its central role in cellular membrane turnover, the molecular basis of how Atg15 is activated and selectively acts on internal membranes has remained elusive. Here, by combining all-atom and coarse-grained molecular dynamics (MD) simulations with in vitro and in vivo analyses, we elucidate the structural and mechanistic principles underlying Atg15 activation and substrate recognition. Our simulations revealed that disulfide bonds are critical for maintaining the structural integrity of the catalytic core, while the C-terminal region locks the catalytic center in a closed state that prevents activation. Membrane binding induces a transition to an open state, enabling catalysis. Through MD-guided mutational analysis, we identified three regions crucial for catalytic locking, membrane binding, and substrate recognition, and experimentally confirmed that mutations in these regions inhibit activity. Furthermore, Atg15 preferentially associates with positively curved membranes, providing a potential basis for its selective action on internal vesicular membranes. These findings suggest that Atg15s activity is controlled through multiple regulatory layers to ensure safe and selective membrane degradation.

cell biology↗

bioRxiv2025

Cargo-directed assembly of nonviral nucleocapsid with controlled size

Precise packaging of diverse cargo within self-assembling protein cages of defined size and shape is essential for many biotechnological applications, yet cellular expression offers limited control over loading. Here, we developed a system for in vitro cargo-directed reconstitution of a split, laboratory evolved nonviral nucleocapsid (spNC-4). Independently expressed and purified spNC- 4 capsid protein subunits were mixed and assembled with cargo molecules in a cooperative manner. As an authentic cargo, mRNA is packaged into a 30 nm-spheric nucleocapsid in vitro, closely matching to spNC-4 expressed in cells. In this system, a diverse range of cargo molecules, including cognate nucleocapsid mRNA, noncognate RNA, RNA complexed with positively supercharged fluorescent protein, and linear double-stranded DNA are encapsulated within the 30 nm-spheric nucleocapsids in vitro. Moreover, the packaging of 30 nm-spherical or rod-shaped DNA origamis as templates induce morphological alterations of the nucleocapsids, resulting in the formation of enlarged 60 nm-spherical structure or rod-shaped structure, respectively. This split-protein, cargo-dependent system provides versatile and programmable control over both composition and architecture of nonviral protein cages, creating a general platform for enzyme nanoreactors, targeted delivery, and vaccine development.

synthetic biology↗

bioRxiv2025

P-body formation is required for yeast proliferation in the phyllosphere

Processing bodies (P-bodies) are major cytosolic ribonucleoprotein granules involved in post-transcriptional regulation. Yeast has been an invaluable model for elucidating the functions of P-bodies under laboratory conditions. However, the physiological significance of P-bodies in natural environments remains unclear. Here, we demonstrate that P-body formation is required for yeast proliferation in the phyllosphere, the aerial parts of plants. Deletion of EDC3, a gene critical for P-body formation, impaired proliferation of the methanol-utilizing yeast Candida boidinii on Arabidopsis thaliana leaves where the yeast assimilates methanol as the carbon source while adapting to changes in environmental conditions. In vitro experiments showed that P-bodies contribute to the spatiotemporal regulation of methanol-induced mRNAs (mimRNAs). These mimRNAs form cytosolic dot structures (termed mimRNA granules) that harbor multiple kinds of mimRNAs. In the edc3{Delta} strain, the formation of mimRNA granules was reduced along with a decrease in mimRNA abundance. Under oxidative stress, colocalization of P-bodies with mimRNA granules markedly increased and growth of the edc3{Delta} strain on methanol was suppressed, suggesting active sequestration of mimRNAs within P-bodies as a stress tolerance response. Time-lapse microscopy revealed dynamic interactions between P-bodies and mimRNAs granules with transient colocalization. Together, our findings indicate that P-bodies function as temporal storage sites where mimRNAs are protected from degradation in the phyllosphere. Impact statementP-bodies support yeast survival on plant leaves by sequestering and protecting methanol-induced mRNAs from degradation

microbiology↗

bioRxiv2025

Fly wounds and tumors restrict macrophages via a matrix degradation-moderating protease inhibitor

Breaches of epithelial homeostasis trigger an inflammatory response. Not only initiation but negative regulation of the response is critical, as autoinflammation can cause tissue damage and chronic disease. Epithelial breaches can be signaled by damage-associated molecular patterns (DAMPs), including basement membrane (BM) degradation, that attract inflammatory cells. Here we show that the conserved thioester-containing protein Tep3 from Drosophila limits innate immune cell attachment to damaged and transformed epithelia. Tep3 is produced in wounds and tumors alongside the matrix metalloprotease MMP1. Tep3 inhibits MMP1 proteolytic activity, reducing production of a BM DAMP that is necessary for macrophage association. A Drosophila tumor upregulates Tep3 to limit an MMP1- and macrophage-dependent anti-tumor immune response, thus accelerating progression and host death. Hence, fly tumors can exploit a physiological anti-inflammatory axis to pathologically limit their immune restriction.

genetics↗

bioRxiv2025

Methylotrophic yeast Candida boidinii enhances the colonization of plant growth-promoting yeast Papiliotrema laurentii in the phyllosphere

Methanol-utilizing microbes are ubiquitous in the phyllosphere, where they assimilate methanol released from pectin, the major component of the plant cell wall. While methylotrophic bacteria Methylobacterium spp. are well studied for their symbiotic relationships with the host plants, the ecology and functional roles of methylotrophic yeasts on plants remain poorly understood. In the effort to isolate yeasts from 26 phyllosphere samples, we identified Candida boidinii as the only methylotrophic yeast, while the remaining isolates, categorized into 17 species in 12 genera, lacked this metabolic trait. To obtain insight into the role of methylotrophic yeasts in the phyllosphere, we investigated the interaction of C. boidinii with a plant growth-promoting yeast (PGPY), Papiliotrema laurentii, one of the identified yeast species during isolation. We found that the colonization of P. laurentii was enhanced by the presence of C. boidinii on Arabidopsis thaliana leaves. Co-cultivation assays revealed that the cell yield of P. laurentii was enhanced by C. boidinii during cultivation on pectin and that the methanol-utilizing ability and pectin methylesterase (PME) activity of C. boidinii contributed to this enhancement. Stable carbon isotope labeling of pectin methylester groups unambiguously confirmed their assimilation by C. boidinii, but not by P. laurentii. These findings suggest that C. boidinii not only survives in the phyllosphere by utilizing pectin-derived methanol but also contributes to the fitness of other yeast species through metabolic cooperation. This study provides new insights into the niche construction and survival strategies of phyllosphere methylotrophic yeasts, highlighting their potential role in shaping microbial community dynamics and promoting beneficial plant-microbe interactions.

microbiology↗

bioRxiv2025

Novel plasmalogen derivative KIT-13 restores neurological function in a mouse model of Rett syndrome by reducing neuroinflammation and restoring mitochondrial function

Neurodevelopmental disorders, including Rett Syndrome (RTT), have no functional cure and cause substantial levels of disability. Neuroinflammation is now strongly associated with both neurodevelopmental disorders and neurodegenerative diseases, providing a strong rationale for development of novel therapeutics targeting common neuroinflammatory mechanisms. RTT is caused by mutations in the methylated DNA binding factor MECP2. Mecp2-deficient (Mecp2-KO) mice, which have been extensively characterized as a mouse model of RTT, exhibit high levels of neuroinflammation, mitochondrial dysfunction, and severe neurological symptoms similar to RTT patients. KIT-13 is a novel plasmalogen derivative being developed for the treatment of neurodevelopmental disorders including RTT. This study evaluated KIT-13 in both cell-based and in vivo models for its potential to inhibit neuroinflammation and address underlying mitochondrial dysfunction, as well as effects on RTT-like neurological symptoms in the RTT mouse model. Oral administration of KIT-13 to Mecp2-KO mice significantly reduced neurological symptoms assessed by a composite score evaluating mobility, gait, hindlimb clasping, tremor, breathing, and general condition and improved the life span of the RTT model mice. In addition, KIT-13 suppressed mitochondrial DNA leakage associated with Mecp2 deficiency, and significantly suppressed neuroinflammation as measured by microglial cell morphology. These results suggest that KIT-13 may be a promising therapeutic agent for RTT and other neuroinflammation-related diseases.

neuroscience↗

bioRxiv2025

Mechanism of bridge-type phospholipid transfer by Atg2 for autophagosome biogenesis

Autophagosome biogenesis requires delivery of millions of phospholipids. In budding yeast, Atg2 and Atg18 couple the ER to the isolation membrane for lipid transport, yet the mechanism is poorly understood. Combining molecular dynamics simulations, in vitro imaging-based lipid transfer assays, and in vivo analyses, we show that Atg1-mediated phosphorylation activates Atg2 as a lipid-transfer bridge. Simulations reveal that Atg2 contains a water-excluding hydrophobic cavity that accommodates [~]25 phospholipids with bilayer-like fluidity. Atg1 phosphorylates an N-terminal helix of Atg2 in vitro and in vivo, thereby opening the ER-facing entrance to the Atg2 cavity and enabling lipid flow between membranes in silico and in vitro. Consistently, phosphodeficient but not phosphomimetic mutations impair autophagy. Cavity narrowing along the conduit disrupts lipid alignment in silico, phosphorylation-activated bridge-type lipid transfer in vitro, and ER-to-isolation-membrane lipophilic dye flow and autophagosome expansion in vivo. These data suggest that Atg1 gates Atg2-mediated bridge-type lipid transport to build autophagosomes.

cell biology↗

bioRxiv2025

Development of visible light-sensitive human OPN5 via single amino acid substitution

Animal opsins, light-sensitive G-protein-coupled receptors (GPCRs), serve as primary light receptors in animals, supporting vision and providing light-dependent regulation of physiology and behaviour. Animal opsins also show great potential to be used as optogenetic tools that regulate cellular G protein signalling with light. Opn5 is a UV-sensitive "non-visual" opsin that is expressed in a wide range of tissues throughout body. Although Opn5 could be a good template for the development of optogenetic tools applicable to tissues outside of the eye because of its broad expression, its sensitivity to poorly tissue-penetrating UV light poses challenges for its application. In this study, we focused on human OPN5 (hOPN5) to attempt to identify amino acid(s) responsible for the UV sensitivity and to shift the spectral sensitivity to visible light. Sequence alignment across UV-sensitive Opn5s identified a conserved lysine reside (Lys91) at a position implicated in spectral tuning in invertebrate opsins. We applied site-directed mutagenesis to replace this residue with neutral (alanine) or acidic (glutamate or aspartate) amino acids. Heterologous action spectroscopy of these mutants revealed substantial shifts in spectral sensitivity (55-63nm) toward visible wavelengths. Our findings identify Lys91 as a key spectral tuning site in hOPN5 and provide visible-light sensitive versions of this protein as a candidate for optogenetic applications.

biophysics↗

bioRxiv2025

A novel sorting method reveals superior metabolic activity of mononucleated over binucleated tetraploid hepatocytes

Hepatocytes display notable ploidy diversity, varying both in the number of genomic copies and in the number of nuclei. Most mouse hepatocytes are tetraploid (4n), which can exist as either mononucleated (1x4n) or binucleated (2x2n) cells. Despite this distinction, these two cell types have traditionally been grouped and studied as a single population. One likely reason for this is that conventional ploidy-sorting methods classify hepatocytes based solely on total DNA content, without distinguishing between mononucleated and binucleated states. In this study, we developed a novel flow cytometry strategy to distinguish and isolate 1x4n and 2x2n hepatocytes. Our approach leverages Hoechst-Area to assess total ploidy and Hoechst-Height to differentiate mononucleated and binucleated hepatocytes. Transcriptome analysis comparing these two populations revealed that 1x4n hepatocytes exhibit a broader and more metabolically active gene expression profile. Importantly, this enhanced metabolic activity was independent of liver zonation, a well-known driver of metabolic heterogeneity in hepatocytes. Our findings uncover a previously underappreciated layer of functional diversity in the liver and provide a new framework for studying the physiological and pathological roles of nuclear configuration in hepatocytes.

cell biology↗

bioRxiv2025

Unsupervised feature computation-based feature selection robustly extracted resting-state functional connectivity patterns related to mental disorders

Research on biomarkers for predicting psychiatric disorders from resting-state functional connectivity (FC) is advancing. While the focus has primarily been on the discriminative performance of biomarkers by machine learning, identification of abnormal FCs in psychiatric disorders has often been treated as a secondary goal. However, it is crucial to investigate the effect size and robustness of the selected FCs because they can be used as potential targets of neurofeedback training or transcranial magnetic stimulation therapy. Here, we incorporated approximately 5,000 runs of resting-state functional magnetic resonance imaging from six datasets, including individuals with three different psychiatric disorders (major depressive disorder [MDD], schizophrenia [SCZ], and autism spectrum disorder [ASD]). We demonstrated that an unsupervised feature-computation-based feature selection method can robustly extract FCs related to psychiatric disorders compared to other conventional supervised feature selection methods. We found that our proposed method robustly extracted FCs with larger effect sizes from the validation dataset compared to different types of feature selection methods based on supervised learning for MDD (Cohens d = 0.40 vs. 0.25), SCZ (0.37 vs. 0.28), and ASD (0.17 vs. 0.16). We found 78, 69, and 81 essential FCs for MDD, SCZ, and ASD, respectively, and these FCs were mainly thalamic and motor network FCs. The current study showed that the unsupervised feature-computation-based feature selection method robustly identified abnormal FCs in psychiatric disorders consistently across datasets. The discovery of such robust FCs will contribute to understanding neural mechanisms as abnormal brain signatures in psychiatric disorders. Furthermore, this finding can aid in developing precise therapeutic interventions, such as neurofeedback training or transcranial magnetic stimulation therapy.

neuroscience↗